Inflammatory Cytokines in Eyes with Uveal Melanoma and Relation with Macrophage Infiltration

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2010 Jun 12

PMID 20538984

Citations 29

Authors

Long V Ly

Inge H G Bronkhorst

Els van Beelen

Johannes Vrolijk

Andrew W Taylor

Mieke Versluis

Gregorius P M Luyten

Martine J Jager

Affiliations

Soon will be listed here.

Abstract

Purpose: The presence of an inflammatory phenotype, characterized by an increased expression of HLA antigens and an immunologic infiltrate, carries a bad prognosis in uveal melanoma. This study was conducted to determine whether the aqueous humor (AqH) from eyes with uveal melanoma contains inflammatory cytokines and whether their presence is associated with inflammation.

Methods: Immediately after enucleation, AqH was obtained from 37 eyes containing uveal melanoma. Samples were stored at -80°C until use. Fifteen different cytokines were measured with a multiplex bead array. Intratumoral macrophages were analyzed by immunohistochemistry and immunofluorescence staining. The presence of specific cytokines was compared with histopathologic, genetic, and clinical tumor characteristics, as well as patient survival.

Results: Several cytokines showed significantly higher expression in the AqH of uveal melanoma-containing eyes than in the AqH of eyes undergoing cataract surgery. MCP-3 was associated with the presence of CD68(+) macrophages. Correlations were found between some cytokine levels and a few known prognostic factors of uveal melanoma, but cytokine levels were not of predictive value for survival.

Conclusions: Uveal melanoma-containing eyes often carry increased levels of inflammation-related cytokines in their AqH. However, the presence of most specific cytokines was not related to the presence of macrophages, clinical or histopathologic parameters, or prognosis.

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References

Curnow S, Murray P . Inflammatory mediators of uveitis: cytokines and chemokines. Curr Opin Ophthalmol. 2006; 17(6):532-7. DOI: 10.1097/ICU.0b013e32801094b5. View

Boyd S, Tan D, Bunce C, Gittos A, Neale M, Hungerford J . Vascular endothelial growth factor is elevated in ocular fluids of eyes harbouring uveal melanoma: identification of a potential therapeutic window. Br J Ophthalmol. 2002; 86(4):448-52. PMC: 1771104. DOI: 10.1136/bjo.86.4.448. View

Virgili G, Gatta G, Ciccolallo L, Capocaccia R, Biggeri A, Crocetti E . Survival in patients with uveal melanoma in Europe. Arch Ophthalmol. 2008; 126(10):1413-8. DOI: 10.1001/archopht.126.10.1413. View

Gragoudas E, Egan K, Seddon J, Glynn R, Walsh S, Finn S . Survival of patients with metastases from uveal melanoma. Ophthalmology. 1991; 98(3):383-9; discussion 390. DOI: 10.1016/s0161-6420(91)32285-1. View

Chang J, McCluskey P, Wakefield D . Acute anterior uveitis and HLA-B27. Surv Ophthalmol. 2005; 50(4):364-88. DOI: 10.1016/j.survophthal.2005.04.003. View

Dearman R, Moussavi A, Kemeny D, Kimber I . Contribution of CD4+ and CD8+ T lymphocyte subsets to the cytokine secretion patterns induced in mice during sensitization to contact and respiratory chemical allergens. Immunology. 1996; 89(4):502-10. PMC: 1456588. DOI: 10.1046/j.1365-2567.1996.d01-778.x. View

Herbeuval J, Lambert C, Sabido O, Cottier M, Fournel P, Dy M . Macrophages from cancer patients: analysis of TRAIL, TRAIL receptors, and colon tumor cell apoptosis. J Natl Cancer Inst. 2003; 95(8):611-21. DOI: 10.1093/jnci/95.8.611. View

Shields C, Materin M, Teixeira L, Mashayekhi A, Ganguly A, Shields J . Small choroidal melanoma with chromosome 3 monosomy on fine-needle aspiration biopsy. Ophthalmology. 2007; 114(10):1919-24. DOI: 10.1016/j.ophtha.2007.04.054. View

Hashimoto M, Hirota K, Yoshitomi H, Maeda S, Teradaira S, Akizuki S . Complement drives Th17 cell differentiation and triggers autoimmune arthritis. J Exp Med. 2010; 207(6):1135-43. PMC: 2882841. DOI: 10.1084/jem.20092301. View

10.

van Kooij B, Rothova A, Rijkers G, De Groot-Mijnes J . Distinct cytokine and chemokine profiles in the aqueous of patients with uveitis and cystoid macular edema. Am J Ophthalmol. 2006; 142(1):192-4. DOI: 10.1016/j.ajo.2006.02.052. View

11.

Sica A, Schioppa T, Mantovani A, Allavena P . Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006; 42(6):717-27. DOI: 10.1016/j.ejca.2006.01.003. View

12.

Cordell J, Falini B, Erber W, Ghosh A, Abdulaziz Z, MacDonald S . Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984; 32(2):219-29. DOI: 10.1177/32.2.6198355. View

13.

Tschentscher F, Husing J, Holter T, Kruse E, Dresen I, Jockel K . Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. Cancer Res. 2003; 63(10):2578-84. View

14.

Makitie T, Summanen P, Tarkkanen A, Kivela T . Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2001; 42(7):1414-21. View

15.

de Waard-Siebinga I, Hilders C, Hansen B, van Delft J, Jager M . HLA expression and tumor-infiltrating immune cells in uveal melanoma. Graefes Arch Clin Exp Ophthalmol. 1996; 234(1):34-42. DOI: 10.1007/BF00186516. View

16.

Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jockel K, Becher R . Prognostic implications of monosomy 3 in uveal melanoma. Lancet. 1996; 347(9010):1222-5. DOI: 10.1016/s0140-6736(96)90736-9. View

17.

Maat W, Jordanova E, van Zelderen-Bhola S, Barthen E, Wessels H, Schalij-Delfos N . The heterogeneous distribution of monosomy 3 in uveal melanomas: implications for prognostication based on fine-needle aspiration biopsies. Arch Pathol Lab Med. 2007; 131(1):91-6. DOI: 10.5858/2007-131-91-THDOMI. View

18.

Kramer M, Monselise Y, Bahar I, Cohen Y, Weinberger D, Goldenberg-Cohen N . Serum cytokine levels in active uveitis and remission. Curr Eye Res. 2007; 32(7-8):669-75. DOI: 10.1080/02713680701523147. View

19.

Midena E, Bonaldi L, Parrozzani R, Tebaldi E, Boccassini B, Vujosevic S . In vivo detection of monosomy 3 in eyes with medium-sized uveal melanoma using transscleral fine needle aspiration biopsy. Eur J Ophthalmol. 2006; 16(3):422-5. DOI: 10.1177/112067210601600310. View

20.

Blom D, Luyten G, Mooy C, Kerkvliet S, Zwinderman A, Jager M . Human leukocyte antigen class I expression. Marker of poor prognosis in uveal melanoma. Invest Ophthalmol Vis Sci. 1997; 38(9):1865-72. View